ArticleNucleic acids research2013
Functional determinants of gate-DNA selection and cleavage by bacterial type II topoisomerases.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Bacterial type II topoisomerases cleave DNA in a species-specific manner.Nucleic acids research · 2026Article
- Distribution of DNA gyrase cleavage sites across the Streptococcus pneumoniae genome: relation to transcription and methylation at GATC sites.Nucleic acids research · 2025Article
- Article
- Highly sensitive mapping of in vitro type II topoisomerase DNA cleavage sites with SHAN-seq.Nucleic acids research · 2024Article
- Highly sensitive mapping ofbioRxiv : the preprint server for biology · 2024Article
- Single-nucleotide resolution detection of Topo IV cleavage activity in theFrontiers in microbiology · 2023Article
- DNA Topoisomerase Inhibitors: Trapping a DNA-Cleaving Machine in Motion.Journal of molecular biology · 2019Review
- Trapping of the transport-segment DNA by the ATPase domains of a type II topoisomerase.Nature communications · 2018Article
- Ubiquitous Nature of Fluoroquinolones: The Oscillation between Antibacterial and Anticancer Activities.Antibiotics (Basel, Switzerland) · 2017Review
- Thiophene antibacterials that allosterically stabilize DNA-cleavage complexes with DNA gyrase.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- The Transcriptome ofFrontiers in microbiology · 2017Review
- Exploring the active site of the Streptococcus pneumoniae topoisomerase IV-DNA cleavage complex with novel 7,8-bridged fluoroquinolones.Open biology · 2016Article
- Structure of a quinolone-stabilized cleavage complex of topoisomerase IV from Klebsiella pneumoniae and comparison with a related Streptococcus pneumoniae complex.Acta crystallographica. Section D, Structural biology · 2016Article
- Reactive Oxygen Species Contribute to the Bactericidal Effects of the Fluoroquinolone Moxifloxacin in Streptococcus pneumoniae.Antimicrobial agents and chemotherapy · 2016Article
- Crystallization and initial crystallographic analysis of covalent DNA-cleavage complexes of Staphyloccocus aureus DNA gyrase with QPT-1, moxifloxacin and etoposide.Acta crystallographica. Section F, Structural biology communications · 2015Article
- Insights into the mechanism of inhibition of novel bacterial topoisomerase inhibitors from characterization of resistant mutants of Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2015Article
- Structure of an 'open' clamp type II topoisomerase-DNA complex provides a mechanism for DNA capture and transport.Nucleic acids research · 2013Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Antibacterial fluoroquinolones trap a cleavage complex of gyrase and topoisomerase (topo) IV inducing site-specific DNA breakage within a bent DNA gate engaged in DNA transport. Despite its importance for drug action and in revealing potential sites of topoisomerase catalysis, the mechanism of DNA selectivity is poorly understood. To explore its functional basis, we generated mutant versions of the strongly cleaved E-site and used a novel competitive assay to examine their gemifloxacin-mediated DNA breakage by Streptococcus pneumoniae topo IV and gyrase. Parallel studies of Ca(2+)-induced cleavage distinguished 'intrinsic recognition' of DNA cleavage sites by topo IV from drug-induced preferences. Analysis revealed strong enzyme-determined requirements for -4G, -2A and -1T bases preceding the breakage site (between -1 and +1) and enzyme-unique or degenerate determinants at -3, plus drug-specific preferences at +2/+3 and for +1 purines associated with drug intercalation. Similar cleavage rules were seen additionally at the novel V-site identified here in ColE1-derived plasmids. In concert with DNA binding data, our results provide functional evidence for DNA, enzyme and drug contributions to DNA cleavage at the gate, suggest a mechanism for DNA discrimination involving enzyme-induced DNA bending/helix distortion and cleavage complex stabilization and advance understanding of fluoroquinolones as important cleavage-enhancing therapeutics.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.